Recent progress on the activation of the cGAS–STING pathway and its regulation by biomolecular condensation  

作　　者：Xiaoyu Yu Zhen Zhao Zhengfan Jiang 

机构地区：[1]Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education,School of Life Sciences,Peking University,Beijing 100871,China [2]Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China

出　　处：《Journal of Molecular Cell Biology》2022年第6期1-13,共13页分子细胞生物学报（英文版）

基　　金：The work is supported by the National Natural Science Foundation of China(31830022 and 81621001);the Chinese Ministry of Science and Technology(2019YFA0508500 and 2020YFA0707800);China Postdoctoral Science Foundation(2021M700242).

摘　　要：The cyclic guanosine monophosphate (GMP)–adenosine monophosphate (AMP) synthetase (cGAS)–stimulator of interferon genes(STING) pathway, comprising the DNA sensor cGAS, the second messenger cyclic GMP–AMP (cGAMP), and the endoplasmicreticulum (ER) adaptor protein STING, detects cytoplasmic double-stranded DNA (dsDNA) to trigger type I-interferon responses forhost defense against pathogens. Previous studies defined a model for the allosteric activation of cGAS by DNA-binding, but recentwork reveals other layers of mechanisms to regulate cGAS activation such as the phase condensation and metal ions, especially thediscovery of Mn^(2+) as a cGAS activator. Activation of the 23-cGAMP sensor STING requires translocating from the ER to the Golgiapparatus. The sulfated glycosaminoglycans at the Golgi are found to be the second STING ligand promoting STING oligomerizationand activation in addition to 23-cGAMP, while surpassed levels of 23-cGAMP induce ER-located STING to form a highly organizedER membranous condensate named STING phase-separator to restrain STING activation. Here, we summarize recent advances in theregulation of cGAS–STING activation and their implications in physiological or pathological conditions, particularly focusing on theemerging complexity of the regulation.

关 键 词：innate immunity cGAS-STING cGAMP manganese(Mn2+) sulfated glycosaminoglycans(sGAGs) biomolecular condensate STING phase-separator 

分 类 号：O62[理学—有机化学]